JC polyomavirus major capsid protein VP1 (JCV VP1)

The JC polyomavirus major capsid protein VP1 is the primary structural component of the JC virus (JCV), a human polyomavirus that remains latent in most of the population but can cause the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals (UniProt P03089). VP1 molecules organize into 72 pentamers to form the icosahedral viral capsid and are responsible for recognizing host cell receptors, specifically alpha-2,6-linked sialic acid on the lactoseries tetrasaccharide c (LSTc) (PubMed: 20538913). This binding is the critical first step for viral attachment and entry into glial cells, such as oligodendrocytes and astrocytes, within the central nervous system (PubMed: 24453376). Because VP1 is the most exposed protein on the virion surface, it serves as the main target for neutralizing antibodies and is a primary focus for the development of vaccines and monoclonal antibody therapies (PubMed: 28834711). Mutations in the surface-exposed loops of VP1 are frequently identified in PML patients; these mutations can alter receptor binding specificity and are thought to facilitate immune evasion and neurovirulence (PubMed: 23698303). While no drugs are currently FDA-approved specifically for targeting JCV VP1, experimental approaches include the use of neutralizing antibodies and small molecules like mefloquine that have shown some inhibitory activity against viral replication in vitro (PubMed: 19667004).

Other names

Major capsid protein VP1VP1JCPyV VP1Polyomavirus JC VP1

Inhibition of viral entry and neutralization of viral particles by blocking the interaction between the VP1 protein and host cell sialic acid receptors.